Endogenous opioid system
What is „endogenous opioid system“?
• System of endogenous substances
with affinity for opioid receptors
• CNS (brain stem, thalamus,
hypothalamus, limbic system,
spinal cord) outside the CNS
(peripheral sensory nerve fibers,
non-myelinated C and myelinated
A fibers, immune system cells)
• Homeostatic and other functions
• Pain
Endogenous opioid peptides
Endogenous opioid peptides
• Endorphins
• Enkephalins
• Dynorphins
• Endomorphins
Precursor peptides
• POMC
• Preproenkephalin
• Preprodynorphin
Opioidmotif
Tyr-Gly-Gly-Phe-(Met/Leu)
Opioid receptors
- DOR –  opioid receptor
- KOR –  opioid receptor
-MOR –  opioid receptor
-NOR – N/OFQ opioid receptor
Transmembrane protein coupled with G protein
Inhibition of neurotransmiter release
Adenylate cyclase
Endorphins
- Alpha, beta, gamma and delta
- Pituitary / hypothalamus and other sites
- Strenuous exercise / physical activity, pain, orgasm
- Analgesia and Feelings of Wellbeing
- Mobilizing the immune system?
- Creating emotional ties
- Food intake
- Same effect in pain but different in stress
 / 
Enkephalins
- Met- / Leu-
CNS sites related to pain perception, behavior, motor control, and
neuroendocrine functions
- T cells, macrophages, mast cells
- Excitement, physical exertion, sexual activity, fear
 / 
Dynorphins
- A and B
- Periaqueductal gray matter, medulla oblongata
- Parts of the spinal cord involved in the transmission of pain
- Hypothalamus, hippocampus, mesencephalon
- Mechanical and thermal hyperalgesia
 / 
Endomorphins
- 1 and 2
- Heterogeneous distribution in CNS
- Antinociceptive function
- NO mediated vasodilation

Nociceptin/orphanin FQ
- Hippocampus, cortex, spinal cord
- It triggers hyperalgesia and allodynia by reversing opioid-induced
analgesia
- Behavior, drug addiction
- Cardiovascular - hypotension / bradycardia
NOP
Physiological functions of EOS
- Stress - b-endorphin binding and ACTH =
connection of both systems
- (+) food intake, effect on food's palatability
- (-) / (+) concentration-dependent fluid intake
- GIT - inhibition of neurotransmitter release constipation
/ reduction of motility
- Renal function (-) - diuresis inhibition (), (-) water
resorption ()
- Memory
- Emotion, mood (+) to euphoric effect
- Sexual behavior - rather (-), (-) socio-sexual
interactions BUT increase sexual arousal and
motivation
- Delivery?
Physiological functions of EOS
- Respiration
- Suppression of respiratory neuron activity - bradypnea?
- Respiratory stress, protective function in hypoxia and hypercapnia
- Cardiovascular function
- In general, inhibitory
- Reduces PF and BP BUT Depends on the Situation!
- Immune function
- Dual effect depending on many factors
- Maybe protection against cancer?